Genetic Predisposition to Hematologic Malignancies in Childhood and Adolescence

Francesco Fabozzi1 and Angela Mastronuzzi1*

1 Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital IRCCS, Rome, Italy

Correspondence to: Dr. Angela Mastronuzzi. Department of Pediatric Hematology/Oncology and Cellular and Gene Therapy, Bambino Gesù Children's Hospital IRCCS, Rome, Italy. E-mail:

Published: May 1, 2023
Received: March 14, 2023
Accepted: April 19, 2023
Mediterr J Hematol Infect Dis 2023, 15(1): e2023032 DOI 10.4084/MJHID.2023.032

This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Advances in molecular biology and genetic testing have greatly improved our understanding of the genetic basis of hematologic malignancies and have enabled the identification of new cancer predisposition syndromes. Recognizing a germline mutation in a patient affected by a hematologic malignancy allows for a tailored treatment approach to minimize toxicities. It informs the donor selection, the timing, and the conditioning strategy for hematopoietic stem cell transplantation, as well as the comorbidities evaluation and surveillance strategies.
This review provides an overview of germline mutations that predispose to hematologic malignancies, focusing on those most common during childhood and adolescence, based on the new International Consensus Classification of Myeloid and Lymphoid Neoplasms.


Advances in molecular biology and genetic technologies have significantly improved our knowledge about the genetic landscape of major cancer types in children and adults.[1] Aside from offering valuable diagnostic and prognostic insights from somatic alterations, assessing non-tumor or germline material using comprehensive sequencing techniques has revolutionized our understanding of how germline mutation affects cancer development. According to several large-scale studies involving pediatric cancer patients, the frequency of potentially harmful germline mutations was estimated to be around 8.5%.[2,3]
Hematologic malignancies represent the most frequent neoplasm affecting children and adolescents, with acute lymphoblastic leukemia (ALL) being the most common type of childhood cancer.[4] In hematologic malignancies, most efforts have focused on identifying acquired genetic alterations to guide prognostic stratification and tailored treatment strategies.[5,6] Although the role of germline genetic alterations in the development of hematologic malignancies has for a long time been underestimated, the inclusion of the category "Myeloid neoplasms with germline predisposition" in the fourth edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic and Lymphoid Tissues has underscored the utmost importance of germline assessment in patients with myeloid tumors.[7] Furthermore, it is becoming increasingly clear that these observations can now be extended to lymphoid malignancies, as demonstrated by the recent International Consensus Classification (ICC) of Myeloid and Lymphoid Neoplasms.[8] Thus, the title is changed from "myeloid neoplasms" to "hematologic neoplasms" with germline predisposition.
Even though many patients lack a family history consistent with a cancer predisposition syndrome,[3] some clues can help us suspect a germline mutation in patients with a hematologic malignancy[6] (Figure 1). In particular, several associated clinical features may point toward specific syndromes (Table 1).[6]

Figure 1 Figure 1. The diagnostic algorithm we propose in the detection of germline mutations in patients with hematologic malignancies. ADA, adenosine deaminase; CBC, complete blood count; DEB, diepoxybutane; FISH, fluorescence in situ hybridization; GI, gastrointestinal; GU,genitourinary; MMC, mitomycin C; SCT, stem cell transplantation.

Table 1 Table 1. Comparison of somatic abnormalities found in germline predisposition syndromes to hematologic malignancies. 

The discovery of a germline mutation in a patient affected by a hematologic malignancy has significant implications, impacting the patient's psychosocial well-being and family relationships, and may lead to important decisions regarding reproductive planning and genetic counseling. Furthermore, it may influence the type and intensity of treatment and the risk of recurrence and secondary cancers. In fact, several of these conditions carry an increased risk of severe toxicity with standard chemotherapy or radiation dosages. Such toxicity can result in prolonged or permanent cytopenias, organ damage, or significant mucositis; thus, early detection of such patients enables tailored treatment using less intense regimens.[6,9] Finally, discovering an inherited mutation in a patient with a hematologic malignancy inevitably impacts the selection of a donor when hematopoietic stem cell transplantation (SCT) is indicated. Even though HLA-matched sibling donors are usually the preferred donors, they may share the same mutation with the affected individual.
Consequently, screening must be performed even if the sibling appears asymptomatic. Several questions also arise regarding the ideal timing for performing SCT as well as the intensity of the conditioning regimen to be preferred, which must be evaluated on a case-by-case basis considering the specific disease.[10] For example, in patients with germline mutations carrying a high penetrance of leukemia, a preemptive SCT may represent a wise option; on the other hand, in cases with a lower probability of developing leukemia, a watch-and-wait strategy may be preferred. Similarly, a reduced-intensity conditioning regimen may benefit patients at high risk of transplant-related toxicities, such as syndromic conditions characterized by numerous comorbidities.
This review provides an overview of genetic mutations predisposing to hematologic malignancies, focusing on those most common among children and young adults. For convenience, we have grouped genes according to the new ICC (Table 2), which includes 4 major subgroups with new entities added in comparison with the 2016 WHO classification: hematologic neoplasms with germline predisposition without a constitutional disorder, including CEBPA, DDX41, and TP53 alterations; those associated with thrombocytopenia or platelet dysfunction including RUNX1, ANKRD26, and ETV6 alterations; those associated with constitutional disorders affecting multiple organ systems including GATA2, SAMD9, and SAMD9L mutations, inherited genetic mutations associated with classic bone marrow failure (BMF) syndromes and juvenile myelomonocytic leukemia (JMML), and Down syndrome; ALL with germline predisposition. These classifications should not be considered rigid as they can sometimes overlap; for example, Down syndrome and germline mutations in ETV6 or TP53 predispose to ALL.

Table 2
Table 2. The ICC of hematologic neoplasms with germline predisposition.

Hematologic neoplasms with germline predisposition without a constitutional disorder affecting multiple organ systems

Myeloid neoplasm with germline CEBPA mutation. CEBPA is a single exon gene in the chromosomal region of 19q13.1 encoding for a granulocyte differentiation factor.[11] Biallelic mutations are often recognized in acute myeloid leukemias (AMLs), defining a unique subtype with good outcome.[12,13] It has been shown that nearly 10% of these cases also carry a germline CEBPA mutation, typically a frameshift or nonsense mutation near the amino terminus of the encoded protein.[14] Progression to AML occurs with a near complete penetrance, often in the second or third decade of life, and may develop without a previous myelodysplastic syndrome (MDS). It is commonly associated with an acquired mutation in the remaining wild-type CEBPA allele.[14,15] One of the peculiar features of this entity is that when these patients have disease recurrence after chemotherapy, they present new clones with a different spectrum of acquired mutations, including new somatic CEBPA mutations, demonstrating that these second leukemias are not true relapses.[15]
Myeloid or lymphoid neoplasms with germline TP53 mutation. TP53 is commonly considered the guardian of the genome, as it plays a pivotal role in the cell cycle, DNA repair, and apoptosis.[16] Germline mutations are the defining feature of Li-Fraumeni syndrome (LFS) and predispose to a diverse range of tumors in adults and children, particularly breast cancer, sarcomas, and brain tumors. In contrast, hematological malignancies are relatively uncommon.[17-19] Leukemias occur with an estimated incidence of 4% and are predominantly hypodiploid ALL and therapy-related myeloid disorders, including AML and MDS.[20-22] In particular, germline TP53 alterations are a hallmark of low hypodiploid ALL, as found in more than half of the children affected.[23] Leukemic transformation is associated with somatic alterations of IKZF2, CDKN2A, and CDKN2B.[23
Due to the very increased susceptibility to second cancers, patients with LFS and a hematological malignancy should avoid exposure to radiation therapy when possible.
Myeloid or lymphoid neoplasms with germline DDX41 mutation. Unlike the other genes cited in this review, germline DDX41 mutations predispose to neoplasm arising during adulthood, typically in the 6th decade.[24-26] These alterations probably underlie more than 5% of AMLs, making them the most common predisposing events reported in AML.[27] Patients carrying DDX41 germline mutations represent a unique AML subset with male sex skewing, older age, low leukocyte count, few somatic genetic events, and high response rates to intensive chemotherapy leading to prolonged survival.[28] A second somatic DDX41 mutation represents the main driver for AML progression.[28] Lymphoid neoplasms have also been described but are less common.[25]

Hematologic neoplasms with germline predisposition associated with a constitutional platelet disorder

Myeloid or lymphoid neoplasms with germline RUNX1 mutation. RUNX1 is a transcription factor that plays a critical role in regulating blood cell development and differentiation, especially involved in megakaryocyte maturation, differentiation, ploidization, and proplatelet formation.[29] Whereas somatic alterations in RUNX1 are among the most common mutations in both adults and children with ALL, AML and MDS, germline mutations define familial platelet disorder with predisposition to myeloid malignancy (FDP-MM), initially described in 1999.[30] Several mutations have been identified to date, including larger gene deletions, nonsense or frameshift mutations, and point mutations acting by haploinsufficiency with dominant negative effects.[31] All these alterations result in an autosomal dominant disorder with a variable penetrance, characterized by quantitative and/or qualitative platelet defects with a predisposition to developing hematological malignancies. The symptomatic patients typically present with mild-to-moderate thrombocytopenia. Platelet morphology is normal but is associated with a severe decrease in platelet aggregation due to decreased dense granules.[31] The risk of malignant transformation into MDS and AML usually occurs in adulthood and is estimated to be 30%-40%;[32] patients carrying RUNX1 mutations with a dominant-negative effect appear to have a higher risk than patients carrying loss-of-function alleles.[31,33] The progression is associated with the acquisition of somatic mutations in the remaining wild-type RUNX1 allele, as well as GATA2 mutations, and less commonly, other genes recurrently mutated in AML and MDS. More rarely, a malignant transformation in other hematological malignancies may occur, T-ALL being the most frequent.[31,34-37]
Myeloid neoplasms with germline ANKRD26 mutation. Gain-of-function single nucleotide substitutions in the ANKRD26 gene, typically in the promoter region, lead to increased gene transcription and signaling through the MPL pathway and impaired proplatelet formation by megakaryocytes.[38] Carriers present with moderate thrombocytopenia, a normal mean platelet volume, and an absent or mild bleeding tendency.[39] The risk of progression to malignancies is estimated at 5% for AML, 2.2% for MDS, and 1.3% for chronic myeloid leukemia (CML).[40]
Myeloid or lymphoid neoplasms with germline ETV6 mutation. ETV6 is a tumor suppressor gene frequently mutated by somatic alterations, such as the ETV6-RUNX1 fusion commonly seen in childhood ALL.[41] Germline mutations are associated with mild to moderate thrombocytopenia with normal-sized platelets and mild to moderate bleeding tendency.[42,43] They can be found in approximately 1% of pediatric ALL cases[44] and are predominantly missense variants. Other than ALLs, ETV6 germline mutations are also associated with MDS/AML, mixed-phenotype acute leukemia, chronic myelomonocytic leukemia (CMML), plasma cell myeloma and polycythemia vera, as well as with solid tumors including colorectal, breast, kidney, and skin cancers, and meningioma.[42,43]

Hematologic neoplasms with germline predisposition associated with a constitutional disorder affecting multiple organ systems

Myeloid neoplasms with germline GATA2 mutation. GATA2 is a transcription factor that plays a leading role in hematopoiesis but can also be expressed in endothelial cells, central nervous system, placenta, fetal liver, and fetal heart.[45,46] This ubiquitous expression is reflected in the wide range of clinical features that patients carrying germline mutations may present, like pulmonary alveolar proteinosis, lymphedema and sensorineural deafness, and miscarriages. However, bone marrow dysfunction represents the hallmark of the disease, leading to recurrent infections (mainly atypical mycobacterial infections and recurrent HPV-related warts) and hematological malignancies.[47-49] Patients carry loss-of-functions mutations, involving mostly the second zinc finger domain and resulting in GATA2 haploinsufficiency.[50] GATA2 deficiency underlies 15% of advanced forms and 7% of all primary MDS in childhood.[51,52] Clinical onset can occur over a highly variable time frame, at a median age of 18 years, whereas some carriers may remain asymptomatic for life though the penetrance at age 60 is 90%.[53] Therefore, intrafamily donor genetic testing, even if asymptomatic, must be warranted before proceeding to SCT. At birth, carriers typically have normal cell counts; however, a progressive reduction of CD34+ cells in bone marrow occurs over time, resulting in monocytopenia, dendritic cell deficiency, NK cell deficiency, B cell deficiency, and, less commonly, neutropenia.[54,55] The progression into MDS is associated with monosomy 7 or trisomy 8,[46,56] whereas progression to AML is frequently driven by ASXL1 alterations.[51] Currently, clear guidelines for managing patients with GATA2 mutations are lacking. A possible algorithm for patient monitoring is proposed in.[57]
Myeloid neoplasms with germline SAMD9 or SAMD9L mutation. Together with GATA2, SAMD9/SAMD9L mutations, two interferon­inducible genes located on chromosome 7, are the most frequent germline mutations in pediatric MDS.[52] They were initially recognized to underlie MIRAGE (Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital phenotypes, and Enteropathy) syndrome and ataxia-pancytopenia syndrome, respectively.[58,59] The penetrance is incomplete, and MDS can also arise in patients without syndromic features.[60] SAMD9/SAMD9L mutations are typically gain-of-function mutations and enhance the effects of the wild-type genes leading to growth arrest when exogenously expressed in cells.[58] The strong selective pressure to not express the mutant allele is responsible for losing the copy of chromosome 7 carrying the altered gene. Together with the SAMD9/SAMD9L gene, several genes on chromosome 7 (e.g., EZH2, SAMD9, SAMD9L, CUX1, and KMT2C) resulted lost, perturbing hematopoiesis and ultimately leading to progression into MDS and AML.[52,58] Importantly, somatic revertant mosaicism that can restore correct hematopoiesis represents another unique feature of SAMD9/9L syndromes. Two main mechanisms have been observed so far: the acquisition of loss-of-function SAMD9/9L mutations neutralizing the gain-of-function germline mutation or an independent uniparental disomy of 7q (UPD7q).[52,56] The timing for performing SCT must be decided on a case-by-case basis, taking into account that children with high expression of the MIRAGE phenotype experience a high rate of transplant-related comorbidities.[61]
Myeloid neoplasms associated with bone marrow failure syndromes. Inherited bone marrow failure syndromes (IBMFS) are a group of various disorders characterized by failure in the production of one or more blood lineages, usually associated with extra hematopoietic abnormalities, that present during childhood in most cases.[62] Different genes involved in diverse cellular functions, including DNA repair, telomere maintenance, and ribosome biogenesis, underlie these disorders (Table 3).

Table 3
Table 3. Inherited bone marrow failure syndromes predisposing to hematological malignancies.

Fanconi Anemia
Fanconi anemia (FA) is a heterogeneous disorder characterized by BMF with a predisposition to AML, increased risk of other solid tumors, growth retardation, and congenital abnormalities, including kidney and urinary tract malformations, thumb and radial ray abnormalities and café au-lait spots.[63-65] It is mostly inherited as an AR trait but can rarely be an X-linked or an AD disorder.[62] Overall, germline mutations affecting 23 genes, all encoding proteins involved in DNA repair, underlie the disease.[62] The cumulative incidence of AML at 40 years is estimated at 15-20%, and the cumulative incidence of MDS at 50 years is 40%.[66] The FANCD1/BRCA2 mutation carriers have a higher risk of developing AML, with a cumulative incidence of 80% at age 10 years.[66] Due to the high toxicity, FA patients suffer when exposed to irradiation and alkylating agents, fludarabine-based conditioning regimens are currently preferred.[62]
Severe congenital neutropenia
Severe peripheral neutropenia (< 0.2 x 10^9/L) is the hallmark of severe congenital neutropenia (SCN), causing an increased risk for recurrent and often life-threatening infections.[67] Several germline mutations can underlie SCN, but it is most commonly caused by AD mutations in ELANE, which encodes neutrophil elastase, and AR mutations in HAX1, involved in the granulocyte-colony stimulating factor signaling pathway.[68,69] SCN patients have a high risk of developing MDS or AML, with a median incidence of 21%.[70,71] Malignant transformation is often driven by acquired mutations in CSF3R (encoding G-CSF receptor) and subsequently in other leukemia-associated genes (such as RUNX1).[72]
Shwachman‑Diamond syndrome
Shwachman-Diamond syndrome (SDS) is usually an AR disorder caused mostly by biallelic mutations in the SBDS gene, encoding a protein involved in ribosome biogenesis.[73] The disease is characterized by exocrine pancreatic insufficiency, BMF, and extra hematopoietic abnormalities such as metaphyseal dysostosis.[62] Patients have a cumulative risk of developing MDS/AML reaching 36% by 30 years of age.[74]
Dyskeratosis congenita and telomere biology disorders
Dyskeratosis congenita (DC) belongs to a spectrum of disorders caused by pathogenic germline variants in telomere biology genes that share a high risk of hematologic and solid malignancies. Only a minority of patients present with the classical triad of mucosal leukoplakia, abnormal skin pigmentation, and nail dystrophy.[75] Most patients carry X-linked pathogenic variants in dyskerin, encoded by DKC1.[76] Other genes were found to underlie these disorders, both AD and AR, while in a significant percentage of cases, the gene responsible is not identified.[77] A cumulative incidence of 2% by age 50 years for leukemia has been reported.[78] When they underwent HSCT, patients with DC suffer from increased transplant-related mortality due to predisposition to both pulmonary and endothelial disease as well as increased susceptibility to alkylating agents and irradiation; therefore, low-intensity fludarabine-based conditioning regimens are currently preferred.[79,80]
Diamond‑Blackfan anemia
Diamond-Blackfan anemia (DBA) is characterized by pure red blood cell aplasia, often associated with congenital anomalies, including thumb abnormalities and short stature.[81,82] Pathogenic AD variants in ribosomal proteins underlie the disease, while X-linked pathogenic mutations in GATA1 can be found in a minority of patients.[62,82] Patients with DBA have an estimated 5-fold increased risk of cancer, including osteogenic sarcoma, colon cancer, and AML.[83]
JMML and related disorders
The ICC separates JMML from adult MDS/MPN. JMML is now considered a genetic entity defined by the presence of molecular alteration of RAS pathway genes,[8] including NRAS, KRAS, PTPN11, NF1, CBL, or rarely RRAS. As might be expected, genetic syndromes associated with germline mutations in these genes, known collectively as Rasopathies, have a significantly increased risk of developing this disease.[84-90] In particular, two JMML subtypes are now defined by germline events in either NF1 or CBL, with malignant progression driven by acquired biallelic inactivation of the respective genes in hematopoietic cells. Importantly, patients harboring germline CBL mutations often experience spontaneous disease resolution, unlike patients with germline NF1 mutations.[87,91-95]
In addition, the ICC distinguishes another entity defined as Noonan syndrome–associated myeloproliferative disorder, associated with germline mutations in PTPN11, KRAS, NRAS, or RIT1. This disorder is characterized by a myeloproliferative disorder occurring in the first year of life and lacking acquired somatic mutations. Although it resembles the typical clinical and hematological parameters of JMML, the disorder generally has a self-limiting course.[90,96-98]
Myeloid or lymphoid neoplasms associated with Down syndrome. Children with Down Syndrome (DS) have an increased risk of developing hematological neoplasms, particularly AML, with nearly a 150-fold increased risk in the first 5 years of life.[99] Morphologically it is commonly a megakaryoblastic AML, with a favorable outcome compared to the counterpart arising in non-DS patients.[100-102] Furthermore, a transient myeloproliferative disorder (TMD) occurs in the neonatal period in 10% of infants with DS, characterized by an accumulation of immature megakaryoblasts in the fetal liver and peripheral blood.[103,104]. Despite TMD regressing, 20-30% of children that experienced TMD will develop DS-AML within the first 4 years of life.[103] A somatic GATA1 mutation is usually found in both TMD and DS-AML.[104-106]
Patients with DS also have an increased incidence of B-ALL, often characterized by alterations in cytokine receptors or kinase signaling pathways (e.g., Philadelphia chromosome-like ALL), notably with CRLF2 dysregulation.[107,108] DS patients are particularly susceptible to treatment-related toxicity, especially with high-dose methotrexate.[109] Consequently, they require tailored therapy with reduced doses of chemotherapy and reduced intensity conditioning regimens when SCT is needed.[110,111]

Acute lymphoblastic leukemia with germline predisposition

Acute lymphoblastic leukemia with a germline PAX5 mutation. PAX5 encodes a transcription factor involved in B-lymphoid lineage maturation, commonly found as a target of somatic alterations in B-ALL.[41,112–114] Germline mutations were recognized in families with increased incidence of B-ALL, inherited as an autosomal dominant trait with variable penetrance.[115,116] B-ALL develops as a result of the loss of 9p containing the wild-type copy.[114]
Acute lymphoblastic leukemia with germline IKZF1 mutation. IKZF1 encodes for IKAROS, a zinc-finger transcription factor that acts as a master transcription regulator in lymphoid development.[117,118] Somatic IKZF1 alterations often occur as secondary events in kinase-driven B-ALL (Ph+ or Ph-like ALL) and DUX4-rearranged ALL.[119,120] Importantly, in kinase-driven ALL, IKZF1 alterations are associated with poor outcome, unlike in DUX4-rearranged.[121-124] Germline mutations have been found in several families affected by immunodeficiency with B-cell lymphopenia and increased incidence of B-ALL.[125-127] Similarly, germline mutations in other members of IKAROS transcription factor, namely IKZF2 and IKZF3, have been recognized as related to immunodeficiency syndromes with immune dysregulation.[128]

Additional germline mutations associated with hematologic neoplasm predispositions

In the context of hereditary syndromes, several germline mutations predispose to the development of hematologic malignancies: Bloom's syndrome (BLM), constitutional mismatch repair deficiency (MLH1, MSH2, MSH6, EPCAM, PMS2), DNMT3A, ERCC6L2, MBD4, Ataxia-Telangiectasia, Nijmegen breakage syndrome, and xeroderma pigmentosum (XPC).[129-138] In addition, hematological malignancies can frequently arise in patients affected by immunodeficiency or immune dysregulation.[139]


The increasingly widespread availability of next-generation sequencing techniques expands the knowledge of the genetic mechanisms underlying cancer development. It enables the identification of a growing number of germline variants associated with hematologic neoplasms. Early identification of these variants at the time of diagnosis allows for personalized treatment and optimized donor selection if SCT is needed. On the other hand, this relatively easy access to genetic information raises some ethical considerations. For example, related donors could not want to know if they carry a pathogenetic germline mutation; however, they may feel forced to do so unwillingly because of pressure from other family members, although they might not be ready to handle the results should they test positive. This situation is even more challenging in the pediatric setting, where consent is expressed by proxy from parents or guardians, and the child, once he or she becomes an adult, may suffer the consequences of decisions not made by himself or herself.[10]


  1. The ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium; Aaltonen, LA; Abascal, F.; Abeshouse, A.; Aburatani, H.; Adams, D.J.; Agrawal, N.; Ahn, KS; Ahn, S.-M.; Aikata, H.; et al. Pan-Cancer Analysis of Whole Genomes. Nature 2020, 578, 82-93, doi:10.1038/s41586-020-1969-6. PMid:32025007 PMCid:PMC7025898
  2. Gröbner, S.N.; Worst, B.C.; Weischenfeldt, J.; Buchhalter, I.; Kleinheinz, K.; Rudneva, V.A.; Johann, P.D.; Balasubramanian, G.P.; Segura-Wang, M.; Brabetz, S.; et al. The Landscape of Genomic Alterations across Childhood Cancers. Nature 2018, 555, 321-327, doi:10.1038/nature25480. PMid:29489754
  3. Zhang, J.; Walsh, M.F.; Wu, G.; Edmonson, M.N.; Gruber, T.A.; Easton, J.; Hedges, D.; Ma, X.; Zhou, X.; Yergeau, D.A.; et al. Germline Mutations in Predisposition Genes in Pediatric Cancer. N. Engl. J. Med. 2015, 373, 2336-2346, doi:10.1056/NEJMoa1508054. PMid:26580448 PMCid:PMC4734119
  4. Pizzo and Poplack's Pediatric Oncology; Blaney, S.M., Adamson, P.C., Helman, L., Eds.; Eighth edition.; Wolters Kluwer Health: Philadelphia, 2021; ISBN 978-1-975124-79-3.
  5. Klco, J.M.; Mullighan, C.G. Advances in Gerline Predisposition to Acute Leukaemias and Myeloid Neoplasms. Nat. Rev. Cancer 2021, 21, 122-137, doi:10.1038/s41568-020-00315-z. PMid:33328584 PMCid:PMC8404376
  6. Furutani, E.; Shimamura, A. Genetic Predisposition to MDS: Diagnosis and Management. Hematol. Am. Soc. Hematol. Educ. Program 2019, 2019, 110-119, doi:10.1182/hematology.2019000021. PMid:31808839 PMCid:PMC6913485
  7. Arber, D.A.; Orazi, A.; Hasserjian, R.; Thiele, J.; Borowitz, M.J.; Le Beau, MM; Bloomfield, C.D.; Cazzola, M.; Vardiman, J.W. The 2016 Revision to the World Health Organization Classification of Myeloid Neoplasms and Acute Leukemia. Blood 2016, 127, 2391-2405, doi:10.1182/blood-2016-03-643544. PMid:27069254
  8. Arber, D.A.; Orazi, A.; Hasserjian, R.P.; Borowitz, M.J.; Calvo, K.R.; Kvasnicka, H.-M.; Wang, S.A.; Bagg, A.; Barbui, T.; Branford, S.; et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: Integrating Morphologic, Clinical, and Genomic Data. Blood 2022, 140, 1200-1228, doi:10.1182/blood.2022015850. PMid:35767897
  9. Rudelius, M.; Weinberg, O.K.; Niemeyer, C.M.; Shimamura, A.; Calvo, K.R. The International Consensus Classification (ICC) of Hematologic Neoplasms with Germline Predisposition, Pediatric Myelodysplastic Syndrome, and Juvenile Myelomonocytic Leukemia. Virchows Arch. 2023, 482, 113-130, doi:10.1007/s00428-022-03447-9. PMid:36445482
  10. Hamilton, K.V.; Maese, L.; Marron, J.M.; Pulsipher, M.A.; Porter, C.C.; Nichols, K.E. Stopping Leukemia in Its Tracks: Should Preemptive Hematopoietic Stem-Cell Transplantation Be Offered to Patients at Increased Genetic Risk for Acute Myeloid Leukemia? J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2019, 37, 2098-2104, doi:10.1200/JCO.19.00181. PMid:31170028
  11. Keeshan, K.; Santilli, G.; Corradini, F.; Perrotti, D.; Calabretta, B. Transcription Activation Function of C/EBPα Is Required for Induction of Granulocytic Differentiation. Blood 2003, 102, 1267-1275, doi:10.1182/blood-2003-02-0477. PMid:12702500
  12. Fröhling, S.; Schlenk, R.F.; Stolze, I.; Bihlmayr, J.; Benner, A.; Kreitmeier, S.; Tobis, K.; Döhner, H.; Döhner, K. CEBPA Mutations in Younger Adults with Acute Myeloid Leukemia and Normal Cytogenetics: Prognostic Relevance and Analysis of Cooperating Mutations. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2004, 22, 624-633, doi:10.1200/JCO.2004.06.060. PMid:14726504
  13. Pabst, T.; Mueller, B.U.; Zhang, P.; Radomska, H.S.; Narravula, S.; Schnittger, S.; Behre, G.; Hiddemann, W.; Tenen, D.G. Dominant-Negative Mutations of CEBPA, Encoding CCAAT/Enhancer Binding Protein-α (C/EBPα), in Acute Myeloid Leukemia. Nat. Genet. 2001, 27, 263-270, doi:10.1038/85820. PMid:11242107
  14. Pabst, T.; Eyholzer, M.; Haefliger, S.; Schardt, J.; Mueller, B.U. Somatic CEBPA Mutations Are a Frequent Second Event in Families with Germline CEBPA Mutations and Familial Acute Myeloid Leukemia. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2008, 26, 5088-5093, doi:10.1200/JCO.2008.16.5563. PMid:18768433
  15. Tawana, K.; Wang, J.; Renneville, A.; Bödör, C.; Hills, R.; Loveday, C.; Savic, A.; Van Delft, F.W.; Treleaven, J.; Georgiades, P.; et al. Disease Evolution and Outcomes in Familial AML with Germline CEBPA Mutations. Blood 2015, 126, 1214-1223, doi:10.1182/blood-2015-05-647172. PMid:26162409
  16. Lane, D.P. P53, Guardian of the Genome. Nature 1992, 358, 15-16, doi:10.1038/358015a0. PMid:1614522
  17. Nigro, J.M.; Baker, S.J.; Preisinger, A.C.; Jessup, J.M.; Hosteller, R.; Cleary, K.; Signer, S.H.; Davidson, N.; Baylin, S.; Devilee, P.; et al. Mutations in the P53 Gene Occur in Diverse Human Tumour Types. Nature 1989, 342, 705-708, doi:10.1038/342705a0. PMid:2531845 
  18. Li, FP; Fraumeni, J.F. Soft-Tissue Sarcomas, Breast Cancer, and Other Neoplasms. A Familial Syndrome? Ann. Intern. Med. 1969, 71, 747-752, doi:10.7326/0003-4819-71-4-747. PMid:5360287
  19. Gonzalez, K.D.; Noltner, K.A.; Buzin, C.H.; Gu, D.; Wen-Fong, C.Y.; Nguyen, V.Q.; Han, J.H.; Lowstuter, K.; Longmate, J.; Sommer, S.S.; et al. Beyond Li Fraumeni Syndrome: Clinical Characteristics of Families with P53 Germline Mutations. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2009, 27, 1250-1256, doi:10.1200/JCO.2008.16.6959. PMid:19204208
  20. Bougeard, G.; Renaux-Petel, M.; Flaman, J.-M.; Charbonnier, C.; Fermey, P.; Belotti, M.; Gauthier-Villars, M.; Stoppa-Lyonnet, D.; Consolino, E.; Brugières, L.; et al. Revisiting Li-Fraumeni Syndrome From TP53 Mutation Carriers. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2015, 33, 2345-2352, doi:10.1200/JCO.2014.59.5728. PMid:26014290
  21. Link, D.C. Identification of a Novel TP53 Cancer Susceptibility Mutation Through Whole-Genome Sequencing of a Patient With Therapy-Related AML. JAMA 2011, 305, 1568, doi:10.1001/jama.2011.473. PMid:21505135 PMCid:PMC3170052
  22. Zebisch, A.; Lal, R.; Müller, M.; Lind, K.; Kashofer, K.; Girschikofsky, M.; Fuchs, D.; Wölfler, A.; Geigl, J.B.; Sill, H. Acute Myeloid Leukemia with TP53 Germ Line Mutations. Blood 2016, 128, 2270-2272, doi:10.1182/blood-2016-08-732610. PMid:27621308 PMCid:PMC5095760
  23. Holmfeldt, L.; Wei, L.; Diaz-Flores, E.; Walsh, M.; Zhang, J.; Ding, L.; Payne-Turner, D.; Churchman, M.; Andersson, A.; Chen, S.-C.; et al. The Genomic Landscape of Hypodiploid Acute Lymphoblastic Leukemia. Nat. Genet. 2013, 45, 242-252, doi:10.1038/ng.2532.5 PMid:23334668 PMCid:PMC3919793
  24. Polprasert, C.; Schulze, I.; Sekeres, M.A.; Makishima, H.; Przychodzen, B.; Hosono, N.; Singh, J.; Padgett, R.A.; Gu, X.; Phillips, J.G.; et al. Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms. Cancer Cell 2015, 27, 658-670, doi:10.1016/j.ccell.2015.03.017. PMid:25920683 PMCid:PMC8713504
  25. Lewinsohn, M.; Brown, A.L.; Weinel, L.M.; Phung, C.; Rafidi, G.; Lee, M.K.; Schreiber, A.W.; Feng, J.; Babic, M.; Chong, C.-E.; et al. Novel Germ Line DDX41 Mutations Define Families with a Lower Age of MDS/AML Onset and Lymphoid Malignancies. Blood 2016, 127, 1017-1023, doi:10.1182/blood-2015-10-676098. PMid:26712909 PMCid:PMC4968341
  26. Li, P.; Brown, S.; Williams, M.; White, T.; Xie, W.; Cui, W.; Peker, D.; Lei, L.; Kunder, C.A.; Wang, H.-Y.; et al. The Genetic Landscape of Germline DDX41 Variants Predisposing to Myeloid Neoplasms. Blood 2022, 140, 716-755, doi:10.1182/blood.2021015135. PMid:35671390
  27. Rio-Machin, A.; Fitzgibbon, J. DDX41 : The Poster Child for Familial AML. Blood 2022, 140, 667-669, doi:10.1182/blood.2022016598. PMid:35980681
  28. Duployez, N.; Largeaud, L.; Duchmann, M.; Kim, R.; Rieunier, J.; Lambert, J.; Bidet, A.; Larcher, L.; Lemoine, J.; Delhommeau, F.; et al. Prognostic Impact of DDX41 Germline Mutations in Intensively Treated Acute Myeloid Leukemia Patients: An ALFA-FILO Study. Blood 2022, 140, 756-768, doi:10.1182/blood.2021015328. PMid:35443031
  29. Bluteau, D.; Glembotsky, A.C.; Raimbault, A.; Balayn, N.; Gilles, L.; Rameau, P.; Nurden, P.; Alessi, M.C.; Debili, N.; Vainchenker, W.; et al. Dysmegakaryopoiesis of FPD/AML Pedigrees with Constitutional RUNX1 Mutations Is Linked to Myosin II Deregulated Expression. Blood 2012, 120, 2708-2718, doi:10.1182/blood-2012-04-422337. PMid:22898599
  30. Song, W.-J.; Sullivan, M.G.; Legare, R.D.; Hutchings, S.; Tan, X.; Kufrin, D.; Ratajczak, J.; Resende, I.C.; Haworth, C.; Hock, R.; et al. Haploinsufficiency of CBFA2 Causes Familial Thrombocytopenia with Propensity to Develop Acute Myelogenous Leukaemia. Nat. Genet. 1999, 23, 166-175, doi:10.1038/13793. PMid:10508512
  31. Latger-Cannard, V.; Philippe, C.; Bouquet, A.; Baccini, V.; Alessi, M.-C.; Ankri, A.; Bauters, A.; Bayart, S.; Cornillet-Lefebvre, P.; Daliphard, S.; et al. Haematological Spectrum and Genotype-Phenotype Correlations in Nine Unrelated Families with RUNX1 Mutations from the French Network on Inherited Platelet Disorders. Orphanet J. Rare Dis. 2016, 11, 49, doi:10.1186/s13023-016-0432-0. PMid:27112265 PMCid:PMC4845427
  32. Owen, C.J.; Toze, C.L.; Koochin, A.; Forrest, D.L.; Smith, C.A.; Stevens, J.M.; Jackson, S.C.; Poon, M.-C.; Sinclair, G.D.; Leber, B.; et al. Five New Pedigrees with Inherited RUNX1 Mutations Causing Familial Platelet Disorder with Propensity to Myeloid Malignancy. Blood 2008, 112, 4639-4645, doi:10.1182/blood-2008-05-156745. PMid:18723428
  33. Michaud, J.; Wu, F.; Osato, M.; Cottles, G.M.; Yanagida, M.; Asou, N.; Shigesada, K.; Ito, Y.; Benson, K.F.; Raskind, W.H.; et al. In Vitro Analyses of Known and Novel RUNX1/AML1 Mutations in Dominant Familial Platelet Disorder with Predisposition to Acute Myelogenous Leukemia: Implications for Mechanisms of Pathogenesis. Blood 2002, 99, 1364-1372, doi:10.1182/blood.v99.4.1364. PMid:11830488
  34. Antony-Debré, I.; Duployez, N.; Bucci, M.; Geffroy, S.; Micol, J.-B.; Renneville, A.; Boissel, N.; Dhédin, N.; Réa, D.; Nelken, B.; et al. Somatic Mutations Associated with Leukemic Progression of Familial Platelet Disorder with Predisposition to Acute Myeloid Leukemia. Leukemia 2016, 30, 999-1002, doi:10.1038/leu.2015.236. PMid:26316320
  35. Churpek, J.E.; Pyrtel, K.; Kanchi, K.-L.; Shao, J.; Koboldt, D.; Miller, C.A.; Shen, D.; Fulton, R.; O'Laughlin, M.; Fronick, C.; et al. Genomic Analysis of Germ Line and Somatic Variants in Familial Myelodysplasia/Acute Myeloid Leukemia. Blood 2015, 126, 2484-2490, doi:10.1182/blood-2015-04-641100. PMid:26492932 PMCid:PMC4661171
  36. Preudhomme, C.; Renneville, A.; Bourdon, V.; Philippe, N.; Roche-Lestienne, C.; Boissel, N.; Dhedin, N.; André, J.-M.; Cornillet-Lefebvre, P.; Baruchel, A.; et al. High Frequency of RUNX1 Biallelic Alteration in Acute Myeloid Leukemia Secondary to Familial Platelet Disorder. Blood 2009, 113, 5583-5587, doi:10.1182/blood-2008-07-168260. PMid:19357396
  37. Shiba, N.; Hasegawa, D.; Park, M.; Murata, C.; Sato-Otsubo, A.; Ogawa, C.; Manabe, A.; Arakawa, H.; Ogawa, S.; Hayashi, Y. CBL Mutation in Chronic Myelomonocytic Leukemia Secondary to Familial Platelet Disorder with Propensity to Develop Acute Myeloid Leukemia (FPD/AML). Blood 2012, 119, 2612-2614, doi:10.1182/blood-2011-02-333435. PMid:22138511
  38. Bluteau, D.; Balduini, A.; Balayn, N.; Currao, M.; Nurden, P.; Deswarte, C.; Leverger, G.; Noris, P.; Perrotta, S.; Solary, E.; et al. Thrombocytopenia-Associated Mutations in the ANKRD26 Regulatory Region Induce MAPK Hyperactivation. J. Clin. Invest. 2014, 124, 580-591, doi:10.1172/JCI71861. PMid:24430186 PMCid:PMC3904625
  39. Noris, P.; Perrotta, S.; Seri, M.; Pecci, A.; Gnan, C.; Loffredo, G.; Pujol-Moix, N.; Zecca, M.; Scognamiglio, F.; De Rocco, D.; et al. Mutations in ANKRD26 Are Responsible for a Frequent Form of Inherited Thrombocytopenia: Analysis of 78 Patients from 21 Families. Blood 2011, 117, 6673-6680, doi:10.1182/blood-2011-02-336537. PMid:21467542
  40. Noris, P.; Favier, R.; Alessi, M.-C.; Geddis, A.E.; Kunishima, S.; Heller, P.G.; Giordano, P.; Niederhoffer, K.Y.; Bussel, J.B.; Podda, G.M.; et al. ANKRD26-Related Thrombocytopenia and Myeloid Malignancies. Blood 2013, 122, 1987-1989, doi:10.1182/blood-2013-04-499319. PMid:24030261
  41. Mullighan, C.G.; Goorha, S.; Radtke, I.; Miller, C.B.; Coustan-Smith, E.; Dalton, J.D.; Girtman, K.; Mathew, S.; Ma, J.; Pounds, S.B.; et al. Genome-Wide Analysis of Genetic Alterations in Acute Lymphoblastic Leukaemia. Nature 2007, 446, 758-764, doi:10.1038/nature05690. PMid:17344859
  42. Zhang, M.Y.; Churpek, J.E.; Keel, S.B.; Walsh, T.; Lee, M.K.; Loeb, K.R.; Gulsuner, S.; Pritchard, C.C.; Sanchez-Bonilla, M.; Delrow, J.J.; et al. Germline ETV6 Mutations in Familial Thrombocytopenia and Hematologic Malignancy. Nat. Genet. 2015, 47, 180-185, doi:10.1038/ng.3177. PMid:25581430 PMCid:PMC4540357
  43. Noetzli, L.; Lo, R.W.; Lee-Sherick, A.B.; Callaghan, M.; Noris, P.; Savoia, A.; Rajpurkar, M.; Jones, K.; Gowan, K.; Balduini, C.L.; et al. Germline Mutations in ETV6 Are Associated with Thrombocytopenia, Red Cell Macrocytosis and Predisposition to Lymphoblastic Leukemia. Nat. Genet. 2015, 47, 535-538, doi:10.1038/ng.3253. PMid:25807284 PMCid:PMC4631613
  44. Moriyama, T.; Metzger, M.L.; Wu, G.; Nishii, R.; Qian, M.; Devidas, M.; Yang, W.; Cheng, C.; Cao, X.; Quinn, E.; et al. Germline Genetic Variation in ETV6 and Risk of Childhood Acute Lymphoblastic Leukaemia: A Systematic Genetic Study. Lancet Oncol. 2015, 16, 1659-1666, doi:10.1016/S1470-2045(15)00369-1. PMid:26522332
  45. Collin, M.; Dickinson, R.; Bigley, V. Haematopoietic and Immune Defects Associated with GATA2 Mutation. Br. J. Haematol. 2015, 169, 173-187, doi:10.1111/bjh.13317. PMid:25707267 PMCid:PMC4409096
  46. Wlodarski, M.W.; Collin, M.; Horwitz, M.S. GATA2 Deficiency and Related Myeloid Neoplasms. Semin. Hematol. 2017, 54, 81-86, doi:10.1053/j.seminhematol.2017.05.002. PMid:28637621 PMCid:PMC5650112
  47. Spinner, M.A.; Sanchez, L.A.; Hsu, A.P.; Shaw, P.A.; Zerbe, C.S.; Calvo, K.R.; Arthur, D.C.; Gu, W.; Gould, C.M.; Brewer, C.C.; et al. GATA2 Deficiency: A Protean Disorder of Hematopoiesis, Lymphatics, and Immunity. Blood 2014, 123, 809-821, doi:10.1182/blood-2013-07-515528. PMid:24227816 PMCid:PMC3916876
  48. Fabozzi, F.; Strocchio, L.; Mastronuzzi, A.; Merli, P. GATA2 and Marrow Failure. Best Pract. Res. Clin. Haematol. 2021, 34, 101278, doi:10.1016/j.beha.2021.101278. PMid:34404529
  49. Fabozzi, F.; Mastronuzzi, A.; Ceglie, G.; Masetti, R.; Leardini, D. GATA 2 Deficiency: Focus on Immune System Impairment. Front. Immunol. 2022, 13. PMid:35769478 PMCid:PMC9234111
  50. Crispino, J.D.; Horwitz, M.S. GATA Factor Mutations in Hematologic Disease. Blood 2017, 129, 2103-2110, doi:10.1182/blood-2016-09-687889. PMid:28179280 PMCid:PMC5391620
  51. Wlodarski, M.W.; Hirabayashi, S.; Pastor, V.; Starý, J.; Hasle, H.; Masetti, R.; Dworzak, M.; Schmugge, M.; van den Heuvel-Eibrink, M.; Ussowicz, M.; et al. Prevalence, Clinical Characteristics, and Prognosis of GATA2-Related Myelodysplastic Syndromes in Children and Adolescents. Blood 2016, 127, 1387-1397, doi:10.1182/blood-2015-09-669937. PMid:26702063
  52. Sahoo, S.S.; Pastor, V.B.; Goodings, C.; Voss, R.K.; Kozyra, E.J.; Szvetnik, A.; Noellke, P.; Dworzak, M.; Starý, J.; Locatelli, F.; et al. Clinical Evolution, Genetic Landscape and Trajectories of Clonal Hematopoiesis in SAMD9/SAMD9L Syndromes. Nat. Med. 2021, 27, 1806-1817, doi:10.1038/s41591-021-01511-6. PMid:34621053 PMCid:PMC9330547
  53. Donadieu, J.; Lamant, M.; Fieschi, C.; de Fontbrune, F.S.; Caye, A.; Ouachee, M.; Beaupain, B.; Bustamante, J.; Poirel, H.A.; Isidor, B.; et al. Natural History of GATA2 Deficiency in a Survey of 79 French and Belgian Patients. Haematologica 2018, 103, 1278-1287, doi:10.3324/haematol.2017.181909. PMid:29724903 PMCid:PMC6068047
  54. Novakova, M.; aliova, M.; Sukova, M.; Wlodarski, M.; Janda, A.; Fro kova, E.; Campr, V.; Lejhancova, K.; Zapletal, O.; Pospi ilova, D.; et al. Loss of B Cells and Their Precursors Is the Most Constant Feature of GATA-2 Deficiency in Childhood Myelodysplastic Syndrome. Haematologica 2016, 101, 707-716, doi:10.3324/haematol.2015.137711. PMid:27013649 PMCid:PMC5013954
  55. Ganapathi, K.A.; Townsley, D.M.; Hsu, A.P.; Arthur, D.C.; Zerbe, C.S.; Cuellar-Rodriguez, J.; Hickstein, D.D.; Rosenzweig, S.D.; Braylan, R.C.; Young, N.S.; et al. GATA2 Deficiency-Associated Bone Marrow Disorder Differs from Idiopathic Aplastic Anemia. Blood 2015, 125, 56-70, doi:10.1182/blood-2014-06-580340. PMid:25359990 PMCid:PMC4281830
  56. Sahoo, SS; Kozyra, E.J.; Wlodarski, M.W. Germline Predisposition in Myeloid Neoplasms: Unique Genetic and Clinical Features of GATA2 Deficiency and SAMD9/SAMD9L Syndromes. Best Pract. Res. Clin. Haematol. 2020, 33, 101197, doi:10.1016/j.beha.2020.101197. PMid:33038986 PMCid:PMC7388796 
  57. Bruzzese, A.; Leardini, D.; Masetti, R.; Strocchio, L.; Girardi, K.; Algeri, M.; Del Baldo, G.; Locatelli, F.; Mastronuzzi, A. GATA2 Related Conditions and Predisposition to Pediatric Myelodysplastic Syndromes. Cancers 2020, 12, 2962, doi:10.3390/cancers12102962. PMid:33066218 PMCid:PMC7602110
  58. Narumi, S.; Amano, N.; Ishii, T.; Katsumata, N.; Muroya, K.; Adachi, M.; Toyoshima, K.; Tanaka, Y.; Fukuzawa, R.; Miyako, K.; et al. SAMD9 Mutations Cause a Novel Multisystem Disorder, MIRAGE Syndrome, and Are Associated with Loss of Chromosome 7. Nat. Genet. 2016, 48, 792-797, doi:10.1038/ng.3569. PMid:27182967
  59. Chen, D.-H.; Below, J.E.; Shimamura, A.; Keel, S.B.; Matsushita, M.; Wolff, J.; Sul, Y.; Bonkowski, E.; Castella, M.; Taniguchi, T.; et al. Ataxia-Pancytopenia Syndrome Is Caused by Missense Mutations in SAMD9L. Am. J. Hum. Genet. 2016, 98, 1146-1158, doi:10.1016/j.ajhg.2016.04.009. PMid:27259050 PMCid:PMC4908176 
  60. Schwartz, J.R.; Ma, J.; Lamprecht, T.; Walsh, M.; Wang, S.; Bryant, V.; Song, G.; Wu, G.; Easton, J.; Kesserwan, C.; et al. The Genomic Landscape of Pediatric Myelodysplastic Syndromes. Nat. Commun. 2017, 8, 1557, doi:10.1038/s41467-017-01590-5. PMid:29146900 PMCid:PMC5691144
  61. Ahmed, I.A.; Farooqi, M.S.; Vander Lugt, M.T.; Boklan, J.; Rose, M.; Friehling, E.D.; Triplett, B.; Lieuw, K.; Saldana, B.D.; Smith, C.M.; et al. Outcomes of Hematopoietic Cell Transplantation in Patients with Germline SAMD9/SAMD9L Mutations. Biol. Blood Marrow Transplant. 2019, 25, 2186-2196, doi:10.1016/j.bbmt.2019.07.007. PMid:31306780 PMCid:PMC7110513
  62. Dokal, I.; Tummala, H.; Vulliamy, T. Inherited Bone Marrow Failure in the Pediatric Patient. Blood 2022, 140, 556-570, doi:10.1182/blood.2020006481. PMid:35605178 PMCid:PMC9373017
  63. Strocchio, L.; Pagliara, D.; Algeri, M.; Li Pira, G.; Rossi, F.; Bertaina, V.; Leone, G.; Pinto, R.M.; Andreani, M.; Agolini, E.; et al. HLA-Haploidentical TCRαβ+/CD19+-Depleted Stem Cell Transplantation in Children and Young Adults with Fanconi Anemia. Blood Adv. 2021, 5, 1333-1339, doi:10.1182/bloodadvances.2020003707. PMid:33656536 PMCid:PMC7948273
  64. Giardino, S.; de Latour, R.P.; Aljurf, M.; Eikema, D.-J.; Bosman, P.; Bertrand, Y.; Tbakhi, A.; Holter, W.; Bornhäuser, M.; Rössig, C.; et al. Outcome of Patients with Fanconi Anemia Developing Myelodysplasia and Acute Leukemia Who Received Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Analysis on Behalf of EBMT Group. Am. J. Hematol. 2020, 95, 809-816, doi:10.1002/ajh.25810. PMid:32267023
  65. Bogliolo, M.; Surrallés, J. Fanconi Anemia: A Model Disease for Studies on Human Genetics and Advanced Therapeutics. Curr. Opin. Genet. Dev. 2015, 33, 32-40, doi:10.1016/j.gde.2015.07.002. PMid:26254775 
  66. Alter, B.P.; Giri, N.; Savage, S.A.; Peters, J.A.; Loud, J.T.; Leathwood, L.; Carr, A.G.; Greene, M.H.; Rosenberg, P.S. Malignancies and Survival Patterns in the National Cancer Institute Inherited Bone Marrow Failure Syndromes Cohort Study: Malignancies and Survival in IBMFS. Br. J. Haematol. 2010, no-no, doi:10.1111/j.1365-2141.2010.08212.x. PMid:20507306 PMCid:PMC3125983 
  67. Skokowa, J.; Dale, D.C.; Touw, I.P.; Zeidler, C.; Welte, K. Severe Congenital Neutropenias. Nat. Rev. Dis. Primer 2017, 3, 17032, doi:10.1038/nrdp.2017.32. PMid:28593997 PMCid:PMC5821468
  68. Dale, D.C.; Person, R.E.; Bolyard, A.A.; Aprikyan, A.G.; Bos, C.; Bonilla, M.A.; Boxer, L.A.; Kannourakis, G.; Zeidler, C.; Welte, K.; et al. Mutations in the Gene Encoding Neutrophil Elastase in Congenital and Cyclic Neutropenia. Blood 2000, 96, 2317-2322. PMid:11001877 
  69. Klein, C.; Grudzien, M.; Appaswamy, G.; Germeshausen, M.; Sandrock, I.; Schäffer, A.A.; Rathinam, C.; Boztug, K.; Schwinzer, B.; Rezaei, N.; et al. HAX1 Deficiency Causes Autosomal Recessive Severe Congenital Neutropenia (Kostmann Disease). Nat. Genet. 2007, 39, 86-92, doi:10.1038/ng1940. PMid:17187068 
  70. Rosenberg, P.S. The Incidence of Leukemia and Mortality from Sepsis in Patients with Severe Congenital Neutropenia Receiving Long-Term G-CSF Therapy. Blood 2006, 107, 4628-4635, doi:10.1182/blood-2005-11-4370. PMid:16497969 PMCid:PMC1895804 
  71. Rosenberg, P.S.; Zeidler, C.; Bolyard, A.A.; Alter, B.P.; Bonilla, M.A.; Boxer, L.A.; Dror, Y.; Kinsey, S.; Link, D.C.; Newburger, P.E.; et al. Stable Long-Term Risk of Leukaemia in Patients with Severe Congenital Neutropenia Maintained on G-CSF Therapy: Short Report. Br. J. Haematol. 2010, no-no, doi:10.1111/j.1365-2141.2010.08216.x. PMid:20456363 PMCid:PMC2906693 
  72. Touw, I.P. Game of Clones: The Genomic Evolution of Severe Congenital Neutropenia. Hematology 2015, 2015, 1-7, doi:10.1182/asheducation-2015.1.1. PMid:26637693 
  73. Warren, A.J. Molecular Basis of the Human Ribosomopathy Shwachman-Diamond Syndrome. Adv. Biol. Regul. 2018, 67, 109-127, doi:10.1016/j.jbior.2017.09.002. PMid:28942353 PMCid:PMC6710477 
  74. Donadieu, J.; Fenneteau, O.; Beaupain, B.; Beaufils, S.; Bellanger, F.; Mahlaoui, N.; Lambilliotte, A.; Aladjidi, N.; Bertrand, Y.; Mialou, V.; et al. Classification of and Risk Factors for Hematologic Complications in a French National Cohort of 102 Patients with Shwachman-Diamond Syndrome. Haematologica 2012, 97, 1312-1319, doi:10.3324/haematol.2011.057489. PMid:22491737 PMCid:PMC3436231 
  75. Calado, R.T.; Young, N.S. Telomere Diseases. N. Engl. J. Med. 2009, 361, 2353-2365, doi:10.1056/NEJMra0903373. PMid:20007561 PMCid:PMC3401586
  76. Heiss, N.S.; Knight, S.W.; Vulliamy, T.J.; Klauck, S.M.; Wiemann, S.; Mason, P.J.; Poustka, A.; Dokal, I. X-Linked Dyskeratosis Congenita Is Caused by Mutations in a Highly Conserved Gene with Putative Nucleolar Functions. Nat. Genet. 1998, 19, 32-38, doi:10.1038/ng0598-32. PMid:9590285 
  77. Dokal, I.; Vulliamy, T.; Mason, P.; Bessler, M. Clinical Utility Gene Card for: Dyskeratosis Congenita - Update 2015. Eur. J. Hum. Genet. EJHG 2015, 23, doi:10.1038/ejhg.2014.170. PMid:25182133 PMCid:PMC4667501
  78. Alter, B.P.; Giri, N.; Savage, S.A.; Rosenberg, P.S. Cancer in the National Cancer Institute Inherited Bone Marrow Failure Syndrome Cohort after Fifteen Years of Follow-Up. Haematologica 2018, 103, 30-39, doi:10.3324/haematol.2017.178111. PMid:29051281 PMCid:PMC5777188
  79. Tummala, H.; Walne, A.; Dokal, I. The Biology and Management of Dyskeratosis Congenita and Related Disorders of Telomeres. Expert Rev. Hematol. 2022, 15, 685-696, doi:10.1080/17474086.2022.2108784. PMid:35929966 
  80. Agarwal, S. Evaluation and Management of Hematopoietic Failure in Dyskeratosis Congenita. Hematol. Oncol. Clin. North Am. 2018, 32, 669-685, doi:10.1016/j.hoc.2018.04.003. PMid:30047419 PMCid:PMC7307713 
  81. Vlachos, A.; Muir, E. How I Treat Diamond-Blackfan Anemia. Blood 2010, 116, 3715-3723, doi:10.1182/blood-2010-02-251090. PMid:20651069 PMCid:PMC2981532
  82. Vlachos, A.; Ball, S.; Dahl, N.; Alter, B.P.; Sheth, S.; Ramenghi, U.; Meerpohl, J.; Karlsson, S.; Liu, J.M.; Leblanc, T.; et al. Diagnosing and Treating Diamond Blackfan Anaemia: Results of an International Clinical Consensus Conference. Br. J. Haematol. 2008, 142, 859-876, doi:10.1111/j.1365-2141.2008.07269.x. PMid:18671700 PMCid:PMC2654478
  83. Vlachos, A.; Rosenberg, P.S.; Atsidaftos, E.; Alter, B.P.; Lipton, J.M. Incidence of Neoplasia in Diamond Blackfan Anemia: A Report from the Diamond Blackfan Anemia Registry. Blood 2012, 119, 3815-3819, doi:10.1182/blood-2011-08-375972. PMid:22362038 PMCid:PMC3335385
  84. Schubbert, S.; Shannon, K.; Bollag, G. Hyperactive Ras in Developmental Disorders and Cancer. Nat. Rev. Cancer 2007, 7, 295-308, doi:10.1038/nrc2109. PMid:17384584
  85. Stiller, C.; Chessells, J.; Fitchett, M. Neurofibromatosis and Childhood Leukaemia/Lymphoma: A Population-Based UKCCSG Study. Br. J. Cancer 1994, 70, 969-972, doi:10.1038/bjc.1994.431. PMid:7947106 PMCid:PMC2033537
  86. Bollag, G.; Clapp, D.W.; Shih, S.; Adler, F.; Zhang, Y.Y.; Thompson, P.; Lange, B.J.; Freedman, M.H.; McCormick, F.; Jacks, T.; et al. Loss of NF1 Results in Activation of the Ras Signaling Pathway and Leads to Aberrant Growth in Haematopoietic Cells. Nat. Genet. 1996, 12, 144-148, doi:10.1038/ng0296-144. PMid:8563751
  87. Locatelli, F.; Niemeyer, C.M. How I Treat Juvenile Myelomonocytic Leukemia. Blood 2015, 125, 1083-1090, doi:10.1182/blood-2014-08-550483. PMid:25564399
  88. Lipka, D.B.; Witte, T.; Toth, R.; Yang, J.; Wiesenfarth, M.; Nöllke, P.; Fischer, A.; Brocks, D.; Gu, Z.; Park, J.; et al. RAS-Pathway Mutation Patterns Define Epigenetic Subclasses in Juvenile Myelomonocytic Leukemia. Nat. Commun. 2017, 8, 2126, doi:10.1038/s41467-017-02177-w. PMid:29259247 PMCid:PMC5736667 
  89. Niemeyer, C.M.; Kang, M.W.; Shin, D.H.; Furlan, I.; Erlacher, M.; Bunin, N.J.; Bunda, S.; Finklestein, J.Z.; Gorr, T.A.; Mehta, P.; et al. Germline CBL Mutations Cause Developmental Abnormalities and Predispose to Juvenile Myelomonocytic Leukemia. Nat. Genet. 2010, 42, 794-800, doi:10.1038/ng.641. PMid:20694012 PMCid:PMC4297285
  90. Niemeyer, C.M.; Flotho, C. Juvenile Myelomonocytic Leukemia: Who's the Driver at the Wheel? Blood 2019, 133, 1060-1070, doi:10.1182/blood-2018-11-844688. PMid:30670449
  91. Yoshida, N.; Yagasaki, H.; Xu, Y.; Matsuda, K.; Yoshimi, A.; Takahashi, Y.; Hama, A.; Nishio, N.; Muramatsu, H.; Watanabe, N.; et al. Correlation of Clinical Features With the Mutational Status of GM-CSF Signaling Pathway-Related Genes in Juvenile Myelomonocytic Leukemia. Pediatr. Res. 2009, 65, 334-340, doi:10.1203/PDR.0b013e3181961d2a. PMid:19047918
  92. Wintering, A.; Dvorak, C.C.; Stieglitz, E.; Loh, M.L. Juvenile Myelomonocytic Leukemia in the Molecular Era: A Clinician's Guide to Diagnosis, Risk Stratification, and Treatment. Blood Adv. 2021, 5, 4783-4793, doi:10.1182/bloodadvances.2021005117. PMid:34525182 PMCid:PMC8759142
  93. Hecht, A.; Meyer, J.A.; Behnert, A.; Wong, E.; Chehab, F.; Olshen, A.; Hechmer, A.; Aftandilian, C.; Bhat, R.; Choi, S.W.; et al. Molecular and Phenotypic Diversity of <I>CBL</I>-Mutated Juvenile Myelomonocytic Leukemia. Haematologica 2020, 107, 178-186, doi:10.3324/haematol.2020.270595. PMid:33375775 PMCid:PMC8719097
  94. Perez, B.; Mechinaud, F.; Galambrun, C.; Ben Romdhane, N.; Isidor, B.; Philip, N.; Derain-Court, J.; Cassinat, B.; Lachenaud, J.; Kaltenbach, S.; et al. Germline Mutations of the CBL Gene Define a New Genetic Syndrome with Predisposition to Juvenile Myelomonocytic Leukaemia. J. Med. Genet. 2010, 47, 686-691, doi:10.1136/jmg.2010.076836. PMid:20543203
  95. Bresolin, S.; Zecca, M.; Flotho, C.; Trentin, L.; Zangrando, A.; Sainati, L.; Stary, J.; de Moerloose, B.; Hasle, H.; Niemeyer, C.M.; et al. Gene Expression-Based Classification as an Independent Predictor of Clinical Outcome in Juvenile Myelomonocytic Leukemia. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2010, 28, 1919-1927, doi:10.1200/JCO.2009.24.4426. PMid:20231685
  96. Strullu, M.; Caye, A.; Lachenaud, J.; Cassinat, B.; Gazal, S.; Fenneteau, O.; Pouvreau, N.; Pereira, S.; Baumann, C.; Contet, A.; et al. Juvenile Myelomonocytic Leukaemia and Noonan Syndrome. J. Med. Genet. 2014, 51, 689-697, doi:10.1136/jmedgenet-2014-102611. PMid:25097206
  97. Hofmans, M.; Schröder, R.; Lammens, T.; Flotho, C.; Niemeyer, C.; Van Roy, N.; Decaluwe, W.; Philippé, J.; De Moerloose, B. Noonan Syndrome‐associated Myeloproliferative Disorder with Somatically Acquired Monosomy 7: Impact on Clinical Decision Making. Br. J. Haematol. 2019, 187, doi:10.1111/bjh.16191. PMid:31617209
  98. O'Halloran, K.; Ritchey, A.K.; Djokic, M.; Friehling, E. Transient Juvenile Myelomonocytic Leukemia in the Setting of PTPN11 Mutation and Noonan Syndrome with Secondary Development of Monosomy 7: O'Halloran et Al. Pediatr. Blood Cancer 2017, 64, e26408, doi:10.1002/pbc.26408. PMid:28084675
  99. Hasle, H.; Clemmensen, I.H.; Mikkelsen, M. Risks of Leukaemia and Solid Tumours in Individuals with Down's Syndrome. The Lancet 2000, 355, 165-169, doi:10.1016/S0140-6736(99)05264-2. PMid:10675114
  100. Creutzig, U.; Ritter, J.; Vormoor, J.; Ludwig, W.D.; Niemeyer, C.; Reinisch, I.; Stollmann-Gibbels, B.; Zimmermann, M.; Harbott, J. Myelodysplasia and Acute Myelogenous Leukemia in Down's Syndrome. A Report of 40 Children of the AML-BFM Study Group. Leukemia 1996, 10, 1677-1686.
  101. Ravindranath, Y.; Abella, E.; Krischer, J.; Wiley, J.; Inoue, S.; Harris, M.; Chauvenet, A.; Alvarado, C.; Dubowy, R.; Ritchey, A. Acute Myeloid Leukemia (AML) in Down's Syndrome Is Highly Responsive to Chemotherapy: Experience on Pediatric Oncology Group AML Study 8498 [See Comments]. Blood 1992, 80, 2210-2214, doi:10.1182/blood.V80.9.2210.2210. PMid:1384797
  102. Lange, B.J.; Kobrinsky, N.; Barnard, D.R.; Arthur, D.C.; Buckley, J.D.; Howells, W.B.; Gold, S.; Sanders, J.; Neudorf, S.; Smith, F.O.; et al. Distinctive Demography, Biology, and Outcome of Acute Myeloid Leukemia and Myelodysplastic Syndrome in Children with Down Syndrome: Children's Cancer Group Studies 2861 and 2891. Blood 1998, 91, 608-615.
  103. Hitzler, JK; Zipursky, A. Origins of Leukaemia in Children with Down Syndrome. Nat. Rev. Cancer 2005, 5, 11-20, doi:10.1038/nrc1525. PMid:15630411
  104. Pine, S.R.; Guo, Q.; Yin, C.; Jayabose, S.; Druschel, C.M.; Sandoval, C. Incidence and Clinical Implications of GATA1 Mutations in Newborns with Down Syndrome. Blood 2007, 110, 2128-2131, doi:10.1182/blood-2007-01-069542. PMid:17576817
  105. Wechsler, J.; Greene, M.; McDevitt, M.A.; Anastasi, J.; Karp, J.E.; Le Beau, MM; Crispino, J.D. Acquired Mutations in GATA1 in the Megakaryoblastic Leukemia of Down Syndrome. Nat. Genet. 2002, 32, 148-152, doi:10.1038/ng955. PMid:12172547
  106. Yoshida, K.; Toki, T.; Okuno, Y.; Kanezaki, R.; Shiraishi, Y.; Sato-Otsubo, A.; Sanada, M.; Park, M.; Terui, K.; Suzuki, H.; et al. The Landscape of Somatic Mutations in Down Syndrome-Related Myeloid Disorders. Nat. Genet. 2013, 45, 1293-1299, doi:10.1038/ng.2759. PMid:24056718
  107. Izraeli, S. The Acute Lymphoblastic Leukemia of Down Syndrome - Genetics and Pathogenesis. Eur. J. Med. Genet. 2016, 59, 158-161, doi:10.1016/j.ejmg.2015.11.010. PMid:26631987
  108. Mullighan, C.G.; Collins-Underwood, J.R.; Phillips, L.A.A.; Loudin, M.G.; Liu, W.; Zhang, J.; Ma, J.; Coustan-Smith, E.; Harvey, R.C.; Willman, C.L.; et al. Rearrangement of CRLF2 in B-Progenitor- and Down Syndrome-Associated Acute Lymphoblastic Leukemia. Nat. Genet. 2009, 41, 1243-1246, doi:10.1038/ng.469. PMid:19838194 PMCid:PMC2783810
  109. Kroll, M.; Kaupat-Bleckmann, K.; Mörickel, A.; Altenl, J.; Schewel, D.M.; Stanullal, M.; Zimmermann, M.; Schrappe, M.; Cario, G. Methotrexate-Associated Toxicity in Children with Down Syndrome and Acute Lymphoblastic Leukemia during Consolidation Therapy with High Dose Methotrexate According to ALL-BFM Treatment Regimen. Haematologica 2020, 105, 1013-1020, doi:10.3324/haematol.2019.224774. PMid:31371414 PMCid:PMC7109740
  110. Muramatsu, H.; Sakaguchi, H.; Taga, T.; Tabuchi, K.; Adachi, S.; Inoue, M.; Kitoh, T.; Suminoe, A.; Yabe, H.; Azuma, E.; et al. Reduced Intensity Conditioning in Allogeneic Stem Cell Transplantation for AML with Down Syndrome: RIC for AML With DS. Pediatr. Blood Cancer 2014, 61, 925-927, doi:10.1002/pbc.24883. PMid:24302531
  111. Shah, N.; Al-Ahmari, A.; Al-Yamani, A.; Dupuis, L.; Stephens, D.; Hitzler, J. Outcome and Toxicity of Chemotherapy for Acute Lymphoblastic Leukemia in Children with down Syndrome: ALL and Down Syndrome Outcomes. Pediatr. Blood Cancer 2009, 52, 14-19, doi:10.1002/pbc.21737. PMid:18802938
  112. Nutt, S.L.; Heavey, B.; Rolink, A.G.; Busslinger, M. Commitment to the B-Lymphoid Lineage Depends on the Transcription Factor Pax5. Nature 1999, 401, 556-562, doi:10.1038/44076. PMid:10524622
  113. Coyaud, E.; Struski, S.; Prade, N.; Familiades, J.; Eichner, R.; Quelen, C.; Bousquet, M.; Mugneret, F.; Talmant, P.; Pages, M.-P.; et al. Wide Diversity of PAX5 Alterations in B-ALL: A Groupe Francophone de Cytogenetique Hematologique Study. Blood 2010, 115, 3089-3097, doi:10.1182/blood-2009-07-234229. PMid:20160164
  114. Gu, Z.; Churchman, M.L.; Roberts, K.G.; Moore, I.; Zhou, X.; Nakitandwe, J.; Hagiwara, K.; Pelletier, S.; Gingras, S.; Berns, H.; et al. PAX5-Driven Subtypes of B-Progenitor Acute Lymphoblastic Leukemia. Nat. Genet. 2019, 51, 296-307, doi:10.1038/s41588-018-0315-5. PMid:30643249 PMCid:PMC6525306
  115. Shah, S.; Schrader, K.A.; Waanders, E.; Timms, A.E.; Vijai, J.; Miething, C.; Wechsler, J.; Yang, J.; Hayes, J.; Klein, R.J.; et al. A Recurrent Germline PAX5 Mutation Confers Susceptibility to Pre-B Cell Acute Lymphoblastic Leukemia. Nat. Genet. 2013, 45, 1226-1231, doi:10.1038/ng.2754. PMid:24013638 PMCid:PMC3919799
  116. Auer, F.; Rüschendorf, F.; Gombert, M.; Husemann, P.; Ginzel, S.; Izraeli, S.; Harit, M.; Weintraub, M.; Weinstein, O.Y.; Lerer, I.; et al. Inherited Susceptibility to Pre B-ALL Caused by Germline Transmission of PAX5 c.547G>A. Leukemia 2014, 28, 1136-1138, doi:10.1038/leu.2013.363. PMid:24287434
  117. Georgopoulos, K.; Bigby, M.; Wang, J.H.; Molnar, A.; Wu, P.; Winandy, S.; Sharpe, A. The Ikaros Gene Is Required for the Development of All Lymphoid Lineages. Cell 1994, 79, 143-156, doi:10.1016/0092-8674(94)90407-3. PMid:7923373
  118. Chen, Q.; Shi, Y.; Chen, Y.; Ji, T.; Li, Y.; Yu, L. Multiple Functions of Ikaros in Hematological Malignancies, Solid Tumor and Autoimmune Diseases. Gene 2019, 684, 47-52, doi:10.1016/j.gene.2018.10.045. PMid:30352248
  119. Mullighan, C.G.; Su, X.; Zhang, J.; Radtke, I.; Phillips, L.A.A.; Miller, C.B.; Ma, J.; Liu, W.; Cheng, C.; Schulman, B.A.; et al. Deletion of IKZF1 and Prognosis in Acute Lymphoblastic Leukemia. N. Engl. J. Med. 2009, 360, 470-480, doi:10.1056/NEJMoa0808253. PMid:19129520 PMCid:PMC2674612
  120. Zhang, J.; McCastlain, K.; Yoshihara, H.; Xu, B.; Chang, Y.; Churchman, M.L.; Wu, G.; Li, Y.; Wei, L.; Iacobucci, I.; et al. Deregulation of DUX4 and ERG in Acute Lymphoblastic Leukemia. Nat. Genet. 2016, 48, 1481-1489, doi:10.1038/ng.3691. PMid:27776115 PMCid:PMC5144107
  121. Den Boer, M.L.; van Slegtenhorst, M.; De Menezes, R.X.; Cheok, M.H.; Buijs-Gladdines, JGCAM; Peters, STCJM; Van Zutven, LJCM; Beverloo, H.B.; Van der Spek, PJ; Escherich, G.; et al. A Subtype of Childhood Acute Lymphoblastic Leukaemia with Poor Treatment Outcome: A Genome-Wide Classification Study. Lancet Oncol. 2009, 10, 125-134, doi:10.1016/S1470-2045(08)70339-5. PMid:19138562
  122. Martinelli, G.; Iacobucci, I.; Storlazzi, C.T.; Vignetti, M.; Paoloni, F.; Cilloni, D.; Soverini, S.; Vitale, A.; Chiaretti, S.; Cimino, G.; et al. IKZF1 (Ikaros) Deletions in BCR-ABL1-Positive Acute Lymphoblastic Leukemia Are Associated with Short Disease-Free Survival and High Rate of Cumulative Incidence of Relapse: A GIMEMA AL WP Report. J. Clin. Oncol. Off. J. Am. Soc. Clin. Oncol. 2009, 27, 5202-5207, doi:10.1200/JCO.2008.21.6408. PMid:19770381
  123. van der Veer, A.; Zaliova, M.; Mottadelli, F.; De Lorenzo, P.; Te Kronnie, G.; Harrison, C.J.; Cavé, H.; Trka, J.; Saha, V.; Schrappe, M.; et al. IKZF1 Status as a Prognostic Feature in BCR-ABL1-Positive Childhood ALL. Blood 2014, 123, 1691-1698, doi:10.1182/blood-2013-06-509794. PMid:24366361
  124. Zaliova, M.; Zimmermannova, O.; Dörge, P.; Eckert, C.; Möricke, A.; Zimmermann, M.; Stuchly, J.; Teigler-Schlegel, A.; Meissner, B.; Koehler, R.; et al. ERG Deletion Is Associated with CD2 and Attenuates the Negative Impact of IKZF1 Deletion in Childhood Acute Lymphoblastic Leukemia. Leukemia 2014, 28, 182-185, doi:10.1038/leu.2013.282. PMid:24072102
  125. Kuehn, H.S.; Boisson, B.; Cunningham-Rundles, C.; Reichenbach, J.; Stray-Pedersen, A.; Gelfand, E.W.; Maffucci, P.; Pierce, K.R.; Abbott, J.K.; Voelkerding, K.V.; et al. Loss of B Cells in Patients with Heterozygous Mutations in IKAROS. N. Engl. J. Med. 2016, 374, 1032-1043, doi:10.1056/NEJMoa1512234. PMid:26981933 PMCid:PMC4836293
  126. Yoshida, N.; Sakaguchi, H.; Muramatsu, H.; Okuno, Y.; Song, C.; Dovat, S.; Shimada, A.; Ozeki, M.; Ohnishi, H.; Teramoto, T.; et al. Germline IKAROS Mutation Associated with Primary Immunodeficiency That Progressed to T-Cell Acute Lymphoblastic Leukemia. Leukemia 2017, 31, 1221-1223, doi:10.1038/leu.2017.25. PMid:28096536
  127. Churchman, M.L.; Qian, M.; Te Kronnie, G.; Zhang, R.; Yang, W.; Zhang, H.; Lana, T.; Tedrick, P.; Baskin, R.; Verbist, K.; et al. Germline Genetic IKZF1 Variation and Predisposition to Childhood Acute Lymphoblastic Leukemia. Cancer Cell 2018, 33, 937-948.e8, doi:10.1016/j.ccell.2018.03.021. PMid:29681510 PMCid:PMC5953820
  128. Shahin, T.; Mayr, D.; Shoeb, M.R.; Kuehn, H.S.; Hoeger, B.; Giuliani, S.; Gawriyski, L.M.; Petronczki, Ö.Y.; Hadjadj, J.; Bal, S.K.; et al. Identification of Germline Monoallelic Mutations in IKZF2 in Patients with Immune Dysregulation. Blood Adv. 2022, 6, 2444-2451, doi:10.1182/bloodadvances.2021006367. PMid:34920454 PMCid:PMC9006292 
  129. Chen, S.; Wang, W.; Lee, S.; Nafa, K.; Lee, J.; Romans, K.; Watson, P.; Gruber, S.B.; Euhus, D.; Kinzler, K.W.; et al. Prediction of Germline Mutations and Cancer Risk in the Lynch Syndrome. JAMA 2006, 296, 1479, doi:10.1001/jama.296.12.1479. PMid:17003396 PMCid:PMC2538673 
  130. Ripperger, T.; Schlegelberger, B. Acute Lymphoblastic Leukemia and Lymphoma in the Context of Constitutional Mismatch Repair Deficiency Syndrome. Eur. J. Med. Genet. 2016, 59, 133-142, doi:10.1016/j.ejmg.2015.12.014. PMid:26743104
  131. Sarasin, A.; Quentin, S.; Droin, N.; Sahbatou, M.; Saada, V.; Auger, N.; Boursin, Y.; Dessen, P.; Raimbault, A.; Asnafi, V.; et al. Familial Predisposition to TP53/Complex Karyotype MDS and Leukemia in DNA Repair-Deficient Xeroderma Pigmentosum. Blood 2019, 133, 2718-2724, doi:10.1182/blood-2019-01-895698. PMid:30914417 PMCid:PMC6610036
  132. Poppe, B.; Van Limbergen, H.; Van Roy, N.; Vandecruys, E.; De Paepe, A.; Benoit, Y.; Speleman, F. Chromosomal Aberrations in Bloom Syndrome Patients with Myeloid Malignancies. Cancer Genet. Cytogenet. 2001, 128, 39-42, doi:10.1016/S0165-4608(01)00392-2. PMid:11454428
  133. Dembowska-Baginska, B.; Perek, D.; Brozyna, A.; Wakulinska, A.; Olczak-Kowalczyk, D.; Gladkowska-Dura, M.; Grajkowska, W.; Chrzanowska, K.H. Non-Hodgkin Lymphoma (NHL) in Children with Nijmegen Breakage Syndrome (NBS). Pediatr. Blood Cancer 2009, 52, 186-190, doi:10.1002/pbc.21789. PMid:18937313
  134. Rafei, H.; DiNardo, C.D. Hereditary Myeloid Malignancies. Best Pract. Res. Clin. Haematol. 2019, 32, 163-176, doi:10.1016/j.beha.2019.05.001. PMid:31203998
  135. Cunniff, C.; Bassetti, J.A.; Ellis, N.A. Bloom's Syndrome: Clinical Spectrum, Molecular Pathogenesis, and Cancer Predisposition. Mol. Syndromol. 2017, 8, 4-23, doi:10.1159/000452082. PMid:28232778 PMCid:PMC5260600
  136. Ferris, M.A.; Smith, A.M.; Heath, S.E.; Duncavage, E.J.; Oberley, M.; Freyer, D.; Wynn, R.; Douzgou, S.; Maris, J.M.; Reilly, A.F.; et al. DNMT3A Overgrowth Syndrome Is Associated with the Development of Hematopoietic Malignancies in Children and Young Adults. Blood 2022, 139, 461-464, doi:10.1182/blood.2021014052. PMid:34788385 PMCid:PMC8777205
  137. Douglas, S.P.M.; Siipola, P.; Kovanen, P.E.; Pyörälä, M.; Kakko, S.; Savolainen, E.-R.; Salmenniemi, U.; Orte, K.; Kytölä, S.; Pitkänen, E.; et al. ERCC6L2 Defines a Novel Entity within Inherited Acute Myeloid Leukemia. Blood 2019, 133, 2724-2728, doi:10.1182/blood-2019-01-896233. PMid:30936069
  138. Ma, S.; E, C.; C, F.; A, Z.; Se, M.; As, AH; A, B.; B, L.; M, R.; T, M.; et al. MBD4 Guards against Methylation Damage and Germ Line Deficiency Predisposes to Clonal Hematopoiesis and Early-Onset AML. Blood 2018, 132, doi:10.1182/blood-2018-05-852566. PMid:30049810 PMCid:PMC6172562
  139. van der Werff Ten Bosch, J.; van den Akker, M. Genetic Predisposition and Hematopoietic Malignancies in Children: Primary Immunodeficiency. Eur. J. Med. Genet. 2016, 59, 647-653, doi:10.1016/j.ejmg.2016.03.001. PMid:26975585